Type I interferons (IFNs) are important in innate and adaptive immunity. They are used to treat virus infections, cancer, and multiple sclerosis (MS). There are 5 type I IFN families in humans-IFN-α with 13 subtypes, plus IFN-β, ɛ, κ, and ω. Because their receptor binding affinities vary, these IFNs have different gene induction profiles and quite variable therapeutic effects. IFN-α subtypes may each be specific for certain viruses, but can be neurotoxic. IFN-β induces IFN-α, plus has additional direct effects on target cells. IFN-β was the first therapy approved that could change the course of MS. It has broader specificity than IFN-α, enhances cognition in MS, and may be neuroprotective and can potentially enhance fertility in women. Priming the IFN signaling system with an injection of IFN-β can enhance subnormal type I IFN signals in MS. Many other commonly used drugs and vitamins may potentiate clinical benefits of IFN-β.